Cassia absus-mediated upregulation of IL-4, IL-10 and downregulation of IL-1ß, IL-6, TNF- α, NF-κB, IFN-γ in CFA-induced arthritis model.

Traditional use of Cassia absus as an anti-inflammatory in conjunctivitis and bronchitis is well reported. Owing to its anti-inflammatory potential, the current study appraised in vivo anti-arthritic activity of n-hexane and aqueous extracts of Cassia absus seeds (200 mg/kg) using Complete Freund's Adjuvant (CFA) rat model of arthritis. Changes in paw size (mm), joint diameter (mm), and pain response (sec) were recorded at the baseline and then after CFA induction at the interval of 4 days till the 28th day. Blood samples of anesthetized rats were collected for the estimation of hematological, oxidative, and inflammatory biomarkers. Results showed percent inhibition in paw edema (45.09% and 60.79%) with both n-hexane and aqueous extracts, respectively. Significant reduction in paw size and ankle joint diameter (P < 0.01) was seen in extracts treated rats. Erythrocyte Sedimentation rate, C-Reactive Protein, White Blood Cell levels significantly lowered, and Hemoglobin, Platelets and Red Blood Cell count significantly increased post-treatments. Superoxide Dismutase, Catalase, and Glutathione were significantly improved (P < 0.0001) in treated groups as compared to CFA induced arthritic control. Real-time polymerase chain reaction investigation showed significant downregulation (P < 0.05) of Interleukin-1ß, Tumor Necrosis Factor-α, Interleukin-6, Cycloxygenase-2, Nuclear Factor-κB, Prostaglandin E Synthase 2, Interferon Gamma and upregulation of Interleukin-4, Interleukin-10 in both n-hexane and aqueous extract-treated groups. It is thereby concluded that Cassia absus can significantly attenuate CFA-induced arthritis by modulation of oxidative and inflammatory biomarkers.

Metabolic Profiling and Investigation of the Modulatory Effect of Fagonia cretica L. Aerial Parts on Hepatic CYP3A4 and UGT2B7 Enzymes in Streptozotocin-Induced Diabetic Model.

Drug-metabolizing enzymes are either boosted or suppressed by diabetes mellitus. This research was designed to explore Fagonia cretica L. aerial parts' impact on CYP3A4 and UGT2B7 activity and their mRNA expression in diabetic rats. Fagonia cretica (F. cretica) dried powder was sequentially extracted with n-hexane, chloroform, ethyl acetate, methanol, and water. The methanol extract and aqueous fraction presented the most significant potential to decrease the concentration of alpha-hydroxyl midazolam, with 176.0 ± 0.85 mg/Kg and 182.9 ± 0.99 mg/Kg, respectively, compared to the streptozotocin (STZ)-induced diabetic group, reflecting the inhibition in CYP3A4 activity. The fold change in mRNA expression of CYP3A4 was decreased significantly by the methanol extract, and the aqueous fraction of F. cretica estimated by 0.15 ± 0.002 and 0.16 ± 0.001, respectively, compared with the diabetic group. Morphine metabolism was significantly increased in rats treated with F. cretica methanol extract and its aqueous fraction, displaying 93.4 ± 0.96 mg/Kg and 96.4 ± 1.27 mg/Kg, respectively, compared with the metabolism of morphine in the diabetic group, which highlights the induction of UGT2B7 activity. The fold change in mRNA expression of UGT2B7 was significantly increased by the methanol extract and the aqueous fraction, estimated at 8.14 ± 0.26 and 7.17 ± 0.23 respectively, compared to the diabetic group. Phytochemical analysis was performed using high-performance liquid chromatography (HPLC), where the methanol extract showed more flavonoids and phenolic compounds compared to the aqueous fraction of F. cretica. The obtained results were further consolidated by molecular docking studies, where quercetin showed the best fitting within the active pocket of CYP3A4, followed by gallic acid, displaying free binding energies (∆G) of -30.83 and -23.12 kcal/mol, respectively. Thus, F. cretica could serve as a complementary medicine with standard anti-diabetic therapy that can modulate the activity of the drug-metabolizing enzymes.

Graphene oxide reinforced silk fibroin nanocomposite as an electroactive interface for the estimation of dopamine.

The fabrication of 2D materials and polymer-based nanocomposites deposited on flexible conductive interfaces has unblocked new horizons to expedite reaction kinetics for developing highly selective and sensitive electrochemical biosensors. Herein, we developed a novel biosensing platform, comprising graphene oxide and a silk fibroin-based nanocomposite, drop-cast on a carbon cloth electrode. The fabricated interface was expected to be a robust and miniaturized sensing platform for precise detection of dopamine (DA). Characterization was performed by SEM, EDX, FTIR, XRD, UV-visible spectroscopy, contact angle measurement, fluorescence spectroscopy, particle size, and zeta potential analysis. CV, EIS, DPV, and chronoamperometry demonstrated the superior electrochemical properties of the working interface and revealed its enhanced active surface area, increased conductivity, and accelerated electron transfer rate. The designed interface exhibited low LoD (0.41 µM), admirable stability, good sensitivity (2.46 µA µM-1 cm-2), wide linearity ranging from 100-900 µM, excellent reproducibility, and superb selectivity against dopamine even in the presence of possible interfering analytes. These findings endorse the feasibility of the practical execution of such an integrated system in real sample analysis.

Interrelated Oncogenic Viruses and Breast Cancer.

Breast Cancer is a multifactorial disease and recent evidence that viruses have a greater role in its aetiology and pathophysiology than previously hypothesized, has garnered a lot of attention in the past couple of years. After the role of Mouse Mammary Tumour Virus (MMTV) in the oncogenesis of breast cancer has been proved in mice, search for similar viruses found quite a plausible relation of Human Papilloma Virus (HPV), Epstein-Barr virus (EBV), and Bovine Leukaemia Virus (BLV) with breast cancer. However, despite practical efforts to provide some clarity in this issue, the evidence that viruses cause breast cancer still remains inconclusive. Therefore, this article aims to clarify some ambiguity and elucidate the correlation of breast cancer and those particular viruses which are found to bring about the development of tumorigenesis by a previous infection or by their own oncogenic ability to manipulate the molecular mechanisms and bypass the immune system of the human body. Although many studies have reported, both, the individual and co-existing presence of HPV, EBV, MMTV, and BLV in patient sample tissues, particularly in Western women, and proposed oncogenic mechanisms, majority of the collective survey of literature fails to provide a delineated and strong conclusive evidence that viruses do, in fact, cause breast cancer. Measures to prevent these viral infections may curb breast cancer cases, especially in the West. More studies are needed to provide a definite conclusion.